Lp-PLA2 activity and mass are associated with increased incidence of ischemic stroke: A population-based cohort study from Malmö, Sweden
Introduction
Atherosclerosis is widely recognized as a chronic inflammatory process, with evidence of inflammation at all stages of disease, from initial plaque formation to destabilization and subsequent rupture [1], [2]. Importantly, blood-borne cells (e.g., monocytes, macrophages, T-lymphocytes) play an important role in promoting the inflammatory processes [1], and epidemiology studies have explored the association between various inflammatory cells, mediators, or markers, and cardiovascular (CV) events (e.g., coronary heart disease [CHD]-related events and ischemic stroke). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is one such novel inflammatory marker associated with several cardiovascular risk factors, low-density lipoprotein cholesterol (LDL), atherosclerotic disease and incident cardiovascular disease (CVD) [3], [4], [5], [6], [7], [8], [9], [10].
The majority of epidemiological studies to date have revealed a positive association between Lp-PLA2 and cardiovascular risk that is independent of traditional (e.g., LDL, blood pressure, smoking, etc.) and emerging (e.g., C-reactive protein [CRP]) risk factors [11], [12], [13], [14], [15]. Of these, only two studies were population-based and included both men and women—the Atherosclerosis Risk in Communities (ARIC) and the Rotterdam studies [11], [12], [14]. A third study, the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) was also population-based, but included only men [13]. Plasma Lp-PLA2 mass was measured in the ARIC study, and there was only a non-significant 15% increase in CHD risk between the highest and lowest tertiles. However, among those with LDL-C levels below the median (130 mg/dL), there was more than a doubling of risk for CHD events between the highest and lowest tertiles, which was statistically significant [11]. In the ARIC study, Lp-PLA2 mass was associated with nearly a two-fold statistically significant increase in ischemic stroke risk [12]. Lp-PLA2 activity was measured in the Rotterdam study, and those with levels in the highest tertile had nearly a two-fold increase for both CHD and stroke events compared with those in the lowest tertile, both statistically significant. In that study, no modification of effect by non-HDL-cholesterol was observed between Lp-PLA2 activity and CVD related events [14].
A strong correlation between Lp-PLA2 mass and activity has been reported in one study [16], but more recent data suggest the correlation may be considerably lower [3], [10]. None of the population-based epidemiology studies to date have explored both Lp-PLA2 activity and mass as markers of cardiovascular risk within the same cohort.
Therefore, the present study was conducted to investigate Lp-PLA2 activity and mass, respectively, associations with incidence CHD or ischemic stroke, respectively, in a large prospective, urban population-based cohort from Malmö, Sweden.
Section snippets
Participants
The Malmö Diet and Cancer Study (MDCS) is a prospective, population-based cohort study designed to explore the effects of diet on cancer risk [17]. All men and women 45–69 years old living in the city of Malmö, Sweden, were eligible for participation. Between October 1991 and February 1994, every other participant was invited to take part in a study of the epidemiology of carotid artery disease [18].
This cardiovascular cohort consisted of 6103 participants (3531 women and 2572 men). The age at
Baseline characteristics
Baseline characteristics between participants who experienced a CHD event, an ischemic stroke and those who did not are shown in Table 1. As compared to those who remained event-free during the follow-up period, cases with ischemic strokes and CHD-related events, respectively, had significantly higher mean blood pressure (140, 152 and 152 mmHg, respectively), mean Lp-PLA2 [both activity (45.0, 49.9 and 50.7 nmol/min/mL, respectively) and mass (268.2, 290.4 and 291.6 ng/mL, respectively] and higher
Discussion
Clinical studies [10], [22] have reported increased levels of Lp-PLA2 in patients with CHD, and population-based studies [11], [12], [13], [14] the relationships between Lp-PLA2 and incidence of cardiovascular disease. Few studies have explored whether increased levels of Lp-PLA2, as assessed as activity or mass within the same cohort, are related to the incidence of CHD and ischemic stroke. The present prospective urban population-based study, of apparently healthy middle-aged Caucasian men
Acknowledgements
This study was supported by grants from the Swedish Medical Research Council, The Swedish Cancer Society, The Swedish Heart and Lung Foundation, GlaxoSmithKline, and the Region of Skane.
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